Actinium-225 (Ac-225, 225Ac), radium-223 (Ra-223, 223Ra)), uranium-230 (U-230, 230U), and bismuth-213 (Bi-213, 213Bi)) are examples of alpha-emitting radionuclides useful for radiation treatment of tumors and other cancers. Actinium-225 in combination with various biomolecules (e.g. antibodies), for example, is a promising system for tumor alpha therapy. FIG. 1 provides a schematic block diagram of the decay of Ac-225, which has a half-life of 10 days (i.e. t1/2=10 d) and undergoes alpha decay to form francium-221. FIG. 2 provides a schematic block diagram of the decay of Ac-227. According to FIG. 1, Francium-221 undergoes alpha decay to form astatine-217, which also undergoes alpha decay to form bismuth-213. A generator system of actinium-225/bismuth-213 provides an accelerator independent source of bismuth-213 for medical applications. Similarly, a generator system of uranium-230 (t1/2=20.8)/thorium-226 (t1/2=31 min) provides an accelerator-independent source of thorium-226, which has potential for the treatment of metastatic disease.
Thorium metal as a target in combination with proton beam irradiation provides a convenient source of protactinium-230, actinium-225, radium-223, and other radionuclides. Table 1 provides a partial listing of radionuclides resulting from irradiation of a thorium target using a proton beam having an incident proton energy of 300 MeV and an internal beam intensity of about 3.5 microamperes (see: Filosofov et al. in “Isolation of radionuclides from thorium targets irradiated with 300 MeV protons,” Radiochemistry, 2013, vol. 55, no. 4, pp. 410-417, incorporated by reference). The radionuclides are listed in order of increasing mass number, along with their corresponding half-lives (t1/2) and production rates.
TABLE 1Half-lifeProductionRadionuclide(t1/2), daysrate, KBq/hBeryllium-753.390Rubidium-8386.250Yttrium-88106.6150Zirconium-9564.04400Niobium-9535.01100Ruthenium-10339.46000Ruthenium-106373.6600Silver-1117.58000Indium-114m49.51000Cadmium-1152.27000Tin-113115.110Tin-117m13.6400Tin-1259.61500Antimony-12460.31300Antimony-12612.43300Tellurium-121m15470Tellurium-123m119.7160Tellurium-127m109.0100Tellurium-129m33.61200Cesium-13613.21200Barium-13111.5500Barium-14012.752200Cerium-139137.6100Cerium-14132.5900Cerium-144284.850Bismuth-20515.3500Bismuth-2066.22300Radium-22311.47000Actinium-22510.06700Thorium-22718.73000
Uranium-230 is a decay product of protactinium-230. Only traces of protactinium occur in nature as protactinium-231 (t1/2=3.28·104 a) and protactinium-234 (t1/2=6.7 h). A well-characterized artificial isotope of protactinium is protactinium-233 (t1/2=27.0 d), which is formed as an intermediate during the production of fissile uranium-233 in thorium fast breeder reactors. The interest in thorium breeder reactors provided an impetus for the recovery of gram-scale quantities of protactinium-233. The element also plays a role both in geochronological dating and nuclear forensics where the system 231Pa/235U is utilized as a chronometer. This chronometer often corresponds with the 230Th/234U decay pair and thus calls for efficient analytical Th/Pa chemical separation techniques.
The isotope protactinium-230 (230Pa, t1/2 17.4 d (days)) partially decays to the alpha emitting radioisotope 230U (t1/220.8 d) may be used for targeted alpha therapy (“TAT”) applications. It may be utilized directly or as a parent of 226Th (t1/2=31 min), analogous to the known 225Ac/213Bi system. Due to the high specific radioactivity of protactinium-230, its recovery from irradiated thorium involves separating relatively small amounts of Pa from a much larger irradiated mass of thorium.
Methods for separating protactinium from thorium have been reported. These methods involve precipitation, solvent extraction, and ion exchange. The main obstacle for separating protactinium from thorium and for subsequent purification of the protactinium is that the most stable valence of protactinium, i.e. Pa(V), does not form simple cations in aqueous solutions. Pa(V) also tends to undergo hydrolysis form polymers. Protactinium(V) also tends to become adsorbed onto most available surfaces.
The availability of alpha radionuclides such as actinium-225, radium-223, and protactinium-230 as a precursor for uranium-230 for radiation therapy does not meet the current need. Both accelerator production methods and efficient bulk chemical recovery methods determine the availability of these isotopes to the user community.
Methods for separating actinium, protactinium, radium, and other radionuclide fission products from proton-irradiated targets of thorium remain desirable. Also desirable are methods for further purification of radionuclide fission products already separated from the bulk of the target (i.e. thorium).